The Role of Calcium in the Action of 5-Hydroxytryptamine and Cyclic Amp on Salivary Glands

1973 ◽  
Vol 58 (2) ◽  
pp. 367-384
Author(s):  
WILLIAM T. PRINCE ◽  
MICHAEL J. BERRIDGE
Keyword(s):  
Cyclic Amp ◽  
Salivary Glands ◽  
Normal Saline ◽  
Mode Of Action ◽  
Apical Membrane ◽  
Potential Response ◽  
Chloride Medium ◽  
Bathing Medium ◽  
Calcium Dependent

1. The role of calcium in the potential and secretory responses of isolated salivary glands of Calliphora to 5-HT and cyclic AMP has been studied. 2. Secretion induced by 5-HT was reversibly inhibited by removal of calcium from the bathing medium. 3. The chloride-dependent depolarization of the apical membrane produced by 5-HT was calcium dependent whereas the potential response to cyclic AMP was little effected. 4. Strontium and barium effectively substituted for calcium. 5. Manganese replaced calcium at the onset of secretory and potential responses but these responses were maintained when manganese was removed. 6. Lanthanum did not substitute for calcium in secretory responses but did inhibit the secretory and potential responses to calcium in calcium-depleted glands. 7. The rate of secretion in a low-chloride medium produced by cyclic AMP was significantly lower than that induced by 5-HT, but there was little difference in normal saline. 8. A model for the mode of action of 5-HT is proposed in which calcium acts as an intracellular intermediary controlling chloride movements whilst cyclic AMP controls a potassium pump.

The Effects of 5-Hydroxytryptamine and Cyclic Amp on the Potential Profile across Isolated Salivary Glands

1972 ◽  
Vol 56 (2) ◽  
pp. 323-333
Author(s):  
WILLIAM T. PRINCE ◽  
MICHAEL J. BERRIDGE
Keyword(s):  
Salivary Gland ◽  
Membrane Potential ◽  
Cyclic Amp ◽  
Salivary Glands ◽  
Apical Membrane ◽  
Basal Membrane ◽  
Potential Profile ◽  
Step Potential ◽  
Bathing Medium ◽  
Transepithelial Potential

1. The sites of the transepithelial potential changes produced by 5-HT and cyclic AMP in the salivary gland of the blowfly (Calliphora) have been investigated. 2. Microelectrodes recorded a two-step potential profile across this epithelium. The cell was negative to both the bathing medium and the saliva. 3. The basal membrane potential was 44·0±0·2 mV and was affected very little by application of either 5-HT or cyclic AMP. 4. The apical membrane was depolarized by 5-HT and in contrast was hyperpolarized by cyclic AMP. 5. On the basis of these results it is concluded that 5-HT has two actions: (a) to stimulate a potassium pump on the apical membrane using cyclic AMP as an intermediary, (b) to increase chloride movement by a mechanism not directly involving cyclic AMP.

The Role of 5-Hydroxytryptamine and Cyclic AMP in the Control of Fluid Secretion by Isolated Salivary Glands

1970 ◽  
Vol 53 (1) ◽  
pp. 171-186 ◽  
Author(s):  
M. J. BERRIDGE
Keyword(s):  
Amino Acids ◽  
Cyclic Amp ◽  
Salivary Glands ◽  
Mode Of Action ◽  
Recovery Time ◽  
Fluid Secretion ◽  
Control Fluid ◽  
Hydrolysis Of ◽  
Derivatives Of

1. Isolated salivary glands of Calliphora have been used as a system on which to study the mode of action of a hormone. 2. Cyclic AMP, which is thought to mediate the action of many different hormones, can stimulate fluid secretion equally as well as 5-HT. 3. Methyl xanthines, which inhibit the hydrolysis of intracellular cyclic AMP by phosphodiesterase, can stimulate secretion and prolong recovery time after removal of 5-HT. 4. Methyl xanthines can sensitize salivary glands to both 5-HT and cyclic AMP. 5. Butyryl derivatives of cyclic AMP can stimulate secretion, but their effect is slower and lasts longer. 6. Certain amino acids and malate support fluid secretion more effectively than trehalose or glucose. 7. It is concluded that cyclic AMP plays an important role in the ability of 5-HT to control fluid secretion by salivary glands.

Studies on the mechanism of fluid secretion by isolated salivary glands of Calliphora

1976 ◽  
Vol 64 (2) ◽  
pp. 311-322
Author(s):  
M. J. Berridge ◽  
B. D. Lindley ◽  
W. T. Prince
Keyword(s):  
Salivary Glands ◽  
Apical Membrane ◽  
Potassium Concentration ◽  
Basal Membrane ◽  
Fluid Secretion ◽  
Sodium Permeability ◽  
Bathing Medium ◽  
Major Cation ◽  
Diuretic Agent ◽  
External Potassium

1. Potassium is the major cation in the secretion of the salivary glands of Calliphora and is necessary for full secretory rates. 2. Other ions (rubidium and sodium) can support secretion in the absence of potassium. 39. During stimulation with 5-HT a Nernst plot of the basal membrane potential has a slope of 53 mV for a tenfold change in external potassium concentration and the slope at rest deviates from this over the range I-20 mM external potassium. 4. Hyperpolarization of the basal membrane by 5-HT is abolished if the chloride in the bathing medium is replaced by isethionate. 5. The diuretic agent amiloride inhibits fluid secretion by a mechanism which may include a reduction in calcium entry in addition to its recognized effect on sodium permeability. 6. A model is proposed in which fluid secretion is driven by the active transport of potassium across the apical membrane with chloride following passively.

Renal transepithelial phosphate secretion: luminal membrane voltage and Ca2+ dependence

1994 ◽  
Vol 267 (4) ◽  
pp. F624-F631 ◽  
Author(s):  
M. Lu ◽  
L. E. Barber ◽  
J. L. Renfro
Keyword(s):  
Kinase Inhibitor ◽  
Apical Membrane ◽  
Electrical Potential ◽  
K Channel ◽  
Bathing Medium ◽  
Calmodulin Antagonist ◽  
Ussing Chambers ◽  
Luminal Membrane ◽  
Renal Proximal Tubule Cells

The role of apical membrane electrical potential, the possibility of K+ channel involvement, and the role of extracellular Ca2+ in transepithelial P(i) secretion were examined in primary monolayer cultures of flounder renal proximal tubule cells in Ussing chambers. Exposure to 200 nM thapsigargin (TG) significantly increased net P(i) secretion. In TG-stimulated tissues, substitution of 100 mM KCl for 100 mM NaCl in the luminal medium depolarized the apical membrane potential from -64 +/- 2.8 to -26 +/- 3.9 mV and strongly inhibited net P(i) secretion. In 32P(i)-preloaded tissues, cell-to-lumen exit of 32P(i) was significantly decreased to approximately 50% of control by high luminal K+ while cell-to-peritubular bath movement was unchanged. Addition of BaCl2 (2 mM) or charybdotoxin (20 nM) to the luminal surface significantly reduced TG-stimulated net P(i) secretion. The elevation of bath Ca2+ from 2 to 5 mM significantly increased secretory flux and decreased reabsorptive flux. The effect of TG on net P(i) secretion was reduced by the Ca2+ channel blocker verapamil (VE, 100 microM) to 65% of control and by calmodulin antagonist W-7 (20 microM) to 35% of control but it was not blocked by the protein kinase inhibitor H-7 (100 microM). VE also significantly inhibited the P(i) secretion induced by acidification of the peritubular bathing medium. The data indicate that transepithelial P(i) secretion induced by TG is significantly influenced by apical membrane electrical polarity, which may be regulated in part by Ca(2+)-activated K+ channels.

Transepithelial Potential Changes During Stimulation of Isolated Salivary Glands with 5-Hydroxytryptamine and Cyclic Amp

1972 ◽  
Vol 56 (1) ◽  
pp. 139-153
Author(s):  
MICHAEL J. BERRIDGE ◽  
WILLIAM T. PRINCE
Keyword(s):  
Cyclic Amp ◽  
Salivary Glands ◽  
Electrical Response ◽  
Cation Transport ◽  
Anion Transport ◽  
Adenyl Cyclase ◽  
Positive Potential ◽  
Dose Dependent ◽  
Stimulation Of

1. The role of cyclic AMP in mediating the action of 5-HT on salivary glands has been studied by measuring transepithelial potentials. 2. The lumen of unstimulated glands is 4 mV positive but becomes 12 mV negative after treatment with 5-HT (10-8M). Both the potential and the secretory responses to 5-HT are dose-dependent over the same concentration range. 3. The electrical response of salivary glands to cyclic AMP is qualitatively different to that of 5-HT; instead of going negative the potential goes more positive. 4. An increase in positive potential is also observed after treatment with theophylline (10-2M), or when glands are stimulated with 5-HT in a chloride-free saline. 5. These results are consistent with the idea that 5-HT has two actions. One is to stimulate the enzyme adenyl cyclase to synthesize cyclic AMP, which, in turn, stimulates cation transport. The other is to increase anion transport by a mechanism which is independent of cyclic AMP.

The electrical response of isolated salivary glands during stimulation with 5-hydroxytryptamine and cyclic AMP

1971 ◽  
Vol 262 (842) ◽  
pp. 111-120 ◽  
Keyword(s):  
Cyclic Amp ◽  
Salivary Glands ◽  
Electrical Response ◽  
Liquid Paraffin ◽  
Fluid Secretion ◽  
Positive Potential ◽  
Bathing Medium ◽  
Gap Technique ◽  
Rapid Changes ◽  
Continuous Potential

Rate of fluid secretion by the salivary glands of the blowfly Calliphora is regulated by 5-hydroxytryptamine (5-HT) working in conjunction with cyclic AMP. Although cyclic AMP can exactly mimic the acceleration of fluid secretion produced by 5-HT, the underlying electrical events are completely different. Transepithelial potentials were measured by a liquid paraffin-gap technique which permits continuous potential recordings during rapid changes of the bathing medium. The potential of the lumen of unstimulated glands is + 5 mV with respect to the bathing medium but becomes — 10 to 20 mV after applying 5-HT. After stimulation with cyclic AMP, however, the luminal potential becomes more positive (+ 30 to 40 mV). A similar effect is obtained with theophylline or when glands are treated with 5-HT in the presence of an impermeant anion such as isethionate. These observations suggest that in addition to stimulating the synthesis of cyclic AMP, 5-HT may also act directly to increase anion movement. Cyclic AMP appears to stimulate cation transport, which explains the increase in positive potential obtained when this compound (or theophylline) is applied in the absence of 5-HT.

scholarly journals Cyclic AMP inhibits Cl-/HCO3- exchange at the apical membrane of Necturus gallbladder epithelium.

1987 ◽  
Vol 90 (2) ◽  
pp. 173-196 ◽  
Author(s):  
L Reuss
Keyword(s):  
Cyclic Amp ◽  
Apical Membrane ◽  
Phosphodiesterase Inhibitor ◽  
Intracellular Camp ◽  
Bathing Solution ◽  
Gallbladder Epithelium ◽  
Bathing Medium ◽  
Necturus Gallbladder ◽  
Mechanism Of Inhibition ◽  
Camp Levels

Intracellular microelectrode techniques were employed to study the effect of cyclic AMP on apical membrane Cl-/HCO3- exchange and electrodiffusive HCO3- transport in Necturus gallbladder epithelium. Intracellular cAMP levels were raised by addition of either the phosphodiesterase inhibitor theophylline (3 X 10(-3) M) or the adenylate cyclase activator forskolin (10(-5) M) to the serosal bathing solution. Measurements of pH in a poorly buffered control mucosal solution upon stopping superfusion show acidification, owing to secretion of both H+ and HCO3-. When the same experiment is performed after addition of amiloride or removal of Na+ from the mucosal bathing medium, alkalinization is observed since H+ transport is either inhibited or reversed, whereas HCO3- secretion persists. The changes in pH in both amiloride or Na-free medium were significantly decreased in theophylline-treated tissues. Theophylline had no effect on the initial rates of fall of intracellular Cl- activity (aCli) upon reducing mucosal solution [Cl-] to either 10 or 0 mM, although membrane voltage and resistance measurements were consistent with stimulation of apical membrane electrodiffusive Cl- permeability. Estimates of the conductive flux, obtained by either reducing simultaneously mucosal [Cl-] and [HCO3-] or lowering [Cl-] alone in the presence of a blocker of anion exchange (diphenylamine-2-carboxylate), indicate that elevation of intracellular cAMP inhibited the anion exchanger by approximately 50%. Measurements of net Cl- uptake upon increasing mucosal Cl- from nominally zero to levels ranging from 2.5 to 100 mM suggest that the mechanism of inhibition is a decrease in Vmax. Consistent with these results, the rate of intracellular alkalinization upon reducing external Cl- was also inhibited significantly by theophylline. Reducing mucosal solution [HCO3-] from 10 to 1 mM under control conditions caused intracellular acidification and an increase in aCli. Theophylline inhibited both changes, by 62 and 32%, respectively. These data indicate that elevation of intracellular cAMP inhibits apical membrane anion (Cl-/HCO3-) exchange. Studies of the effects of rapid changes in mucosal [HCO3-] on membrane voltages and the apparent ratio of membrane resistances, both in the presence and in the absence of theophylline, with or without Cl- in the mucosal solution, do not support the hypothesis that cAMP produces a sizable increase in apical membrane electrodiffusive HCO3- permeability.

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